Effect of remote ischaemic conditioning on clinical outcomes in patients with acute myocardial infarction (CONDI-2/ERIC-PPCI): a single-blind randomised controlled trial.

BACKGROUND: Remote ischaemic conditioning with transient ischaemia and reperfusion applied to the arm has been shown to reduce myocardial infarct size in patients with ST-elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PPCI). We investigated whether remote ischaemic conditioning could reduce the incidence of cardiac death and hospitalisation for heart failure at 12 months. METHODS: We did an international investigator-initiated, prospective, single-blind, randomised controlled trial (CONDI-2/ERIC-PPCI) at 33 centres across the UK, Denmark, Spain, and Serbia. Patients (age >18 years) with suspected STEMI and who were eligible for PPCI were randomly allocated (1:1, stratified by centre with a permuted block method) to receive standard treatment (including a sham simulated remote ischaemic conditioning intervention at UK sites only) or remote ischaemic conditioning treatment (intermittent ischaemia and reperfusion applied to the arm through four cycles of 5-min inflation and 5-min deflation of an automated cuff device) before PPCI. Investigators responsible for data collection and outcome assessment were masked to treatment allocation. The primary combined endpoint was cardiac death or hospitalisation for heart failure at 12 months in the intention-to-treat population. This trial is registered with ClinicalTrials.gov (NCT02342522) and is completed. FINDINGS: Between Nov 6, 2013, and March 31, 2018, 5401 patients were randomly allocated to either the control group (n=2701) or the remote ischaemic conditioning group (n=2700). After exclusion of patients upon hospital arrival or loss to follow-up, 2569 patients in the control group and 2546 in the intervention group were included in the intention-to-treat analysis. At 12 months post-PPCI, the Kaplan-Meier-estimated frequencies of cardiac death or hospitalisation for heart failure (the primary endpoint) were 220 (8·6%) patients in the control group and 239 (9·4%) in the remote ischaemic conditioning group (hazard ratio 1·10 [95% CI 0·91-1·32], p=0·32 for intervention versus control). No important unexpected adverse events or side effects of remote ischaemic conditioning were observed. INTERPRETATION: Remote ischaemic conditioning does not improve clinical outcomes (cardiac death or hospitalisation for heart failure) at 12 months in patients with STEMI undergoing PPCI. FUNDING: British Heart Foundation, University College London Hospitals/University College London Biomedical Research Centre, Danish Innovation Foundation, Novo Nordisk Foundation, TrygFonden

Poor relationship between exercise capacity and spirometric measurements in patients with more symptomatic heart failure

Background: The origin of exercise limitation in patients with chronic heart failure (CHF) is multifactorial, and the relative contributions of different abnormalities may vary with severity of heart failure symptoms. The aim of the current study was to determine the extent to which spirometric indices predict peak exercise capacity in patients with differing severity of symptoms. Methods and Results: A total of 340 patients with left ventricular systolic dysfunction underwent spirometry, and a ramped, maximal exercise treadmill test with metabolic gas exchange measurements. For comparative purposes, a group of 174 aged-matched controls with no major structural heart disease (MSHD) was also included. In a stepwise linear regression model, forced expiratory volume in 1 second (FEV 1 ) and forced vital capacity (FVC) were independent predictors of peak oxygen uptake (pV̇O 2 ) in controls (r 2 = 18-25%; P = .001) and New York Heart Association (NYHA) I-II patients (r 2 = 16-18%; P = .001). No association between spirometric indices (FEV 1 /FVC) and pV̇O 2 (r 2 = 1-2%; P > .05) was found in NYHA III-IV patients. Conclusion: In aged-matched controls with no MSHD, spirometric variables (FEV 1 /FVC) explain 18% to 25% of the variance in pV̇O 2 , and 16% to 18% of the variance in patients with NYHA class I-II symptoms. As symptoms worsen, the influence of spirometric variables on peak exercise capacity diminishes, and there is no such relation in the NYHA class III-IV patients. © 2005 Elsevier Inc. All rights reserved

A comparison between monophasic and biphasic defibrillation for the cardioversion of persistent atrial fibrillation in patients with and without heart failure

Aims: Atrial fibrillation (AF) and heart failure commonly coexist. Restoring sinus rhythm using external direct current cardioversion (DCCV) may improve left ventricular function, exercise capacity and quality of life (QoL). However, DCCV may be less successful at restoring sinus rhythm in patients with heart failure. We aimed to determine whether biphasic DCCV was superior to monophasic DCCV for the restoration of sinus rhythm in patients with heart failure. Methods: 592 consecutive cardioversion procedures were performed on 503 patients for persistent AF, 261 (44%) procedures using monophasic defibrillation and 331 (56%) using biphasic. Patients with symptomatic heart failure were identified for further analysis. Results: 173 cardioversions were performed on 149 patients with heart failure. The overall success rate of cardioversion in this group was 82.7% (83.3% and 82.2% for monophasic and biphasic respectively). There was no difference in the success rate of cardioversion for those with heart failure compared to those without heart failure (p = 0.141). Furthermore, there was no substantial difference in success rates according to defibrillation type (83.3% v. 84.2% for monophasic and 82.2% v. 88.5% for biphasic, p = 0.502 and 0.085 respectively). Conclusion: External defibrillation is similarly effective at restoring SR in patients with and without HF and both mono- and biphasic shocks have a high rate of success. However, significantly less energy (maximal and cumulative) is required to restore SR using biphasic defibrillation

The reproducibility and sensitivity of the 6-min walk test in elderly patients with chronic heart failure

Aims: The 6-min walk test (6-MWT) is used to estimate functional capacity. However, in elderly patients with chronic heart failure (CHF): (i) 1 year reproducibility of the 6-MWT; (ii) sensitivity of the 6-MWT to self-perceived changes in symptoms of heart failure; and (iii) implications for patient numbers required for studies using the 6-MWT as an endpoint have not been described. Methods and results: One thousand and seventy-seven patients with CHF, aged > 60, with NYHA Class ≥II were recruited. Heart failure symptom assessment was determined using a questionnaire related to aspects of physical function, and patients performed a baseline 6-MWT, with follow-up 1 year later. Seventy-four patients with unchanged symptoms had an unchanged 6-MWT distance, with an overall intraclass correlation coefficient of 0.80 (95% CI = 0.69-0.87). Four hundred and twenty-three patients reported an improvement in symptoms during follow-up. There was a negative correlation (r = -0.55; P = 0.0001) between Δ symptoms and Δ 6-MWT (i.e. a reduced 6-MWT distance is associated with reduced symptom severity at follow-up). Five hundred and sixteen patients reported worsening symptoms of heart failure, a moderate inverse correlation (r = -0.53; P = 0.0001) was displayed between Δ symptoms and Δ 6-MWT. For all patients, irrespective of symptom status, a high inverse correlation (r = -0.75; P = 0.0001) was evident. On the basis of the data for patients with unchanged symptoms, it is calculated that to detect an increase in 6-MWT of 50 m, with 90% power, a study size of approximately 120 is required. Conclusion: In elderly patients with CHF, the 6-MWT shows satisfactory agreement when repeated 1 year later. Change in 6-MWT distance is sensitive to change in self-perceived symptoms of heart failure. © The European Society of Cardiology 2005. All rights reserved

Cardiac output does not limit submaximal exercise capacity in patients with chronic heart failure

AimsMechanisms of exercise limitation in patients with chronic heart failure (CHF) are incompletely understood. During matched submaximal, fixed-rate exercise, oxygen uptake is similar in patients and healthy controls. However, the importance of cardiac output (CO) remains unresolved. We aimed to determine the effect of submaximal exercise on CO and other haemodynamic variables in patients with CHF using a validated non-invasive inert gas rebreathing system.Methods and resultsSeventy-two subjects with a mean age (±SD) of 68.2 (±8.1) years, performed fixed-rate exercise for 3 min at 15,30, 45, and 60 W workloads on a cycle ergometer. Cardiac output/index (CI) and oxygen uptake (VO2) were determined at each stage by inert gas rebreathing. Subjects with systolic HF (n = 27) were compared with those without (n = 45). Cardiac index was lower in subjects with CHF at rest and throughout exercise. VO2 was the same for both groups at rest and during exercise. There was no difference in the relative or absolute increase in CI from rest to 60 W (1.70 ± 0.69 vs. 1.99 ± 0.56 L/min/m 2 , P = 0.102, respectively). Arterio-venous O2 saturation difference at peak exercise was 75.4 ± 10.4 vs. 63.0 ± 12.1, P = 0.001, for CHF and non-CHF subjects, respectively. ConclusionDuring submaximal exercise, patients with systolic heart failure are able to increase their CO to a similar extent as those without; with equal levels of oxygen consumption, but requiring a much greater degree of tissue oxygen extraction. © 2010 The Author